rs147373451

This variant is located in the NOTCH3 gene.

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

neurogenic locus notch homolog protein 3 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 1.07
p 5.0e-114
N 47,745
Large GWAS
European
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ClinVar annotation

Likely Benign★★★☆
14 submitters20 publications

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1; not specified; not provided; Lateral meningocele syndrome;Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1;Myofibromatosis, infantile, 2; NOTCH3-related disorder

View on ClinVar →
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Research that mentions this SNP (2)

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Association study of the serotoninergic system in migraine in the spanish population
FunctionalN=149Corominas R. et al.(2010)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Development and validation of a targeted NGS panel for diagnosing familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), CADASIL, and migraine with aura. In 149 patients across 4 cohorts (55 FHM, 44 CADASIL, 31 EA2, 19 migraine families), the panel identified novel and known mutations in genes CACNA1A, ATP1A2, SCN1A, and NOTCH3, increasing mutation detection rate from 7.7% to 28.5%. Notably, ATP1A2 and NOTCH3 mutations were identified in typical migraine with aura families for the first time, demonstrating aetiological overlap with FHM.

Traits studied:CADASILEpisodic Ataxia Type 2Familial Hemiplegic MigraineMigraine with auraMigraine without auraSpinocerebellar ataxia type 6
PubMedDOIMetascience Observatory
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Usher syndrome type 1 due to missense mutations on bothCDH23 alleles: investigation of mRNA splicing
AssociationN=1,725Elvir Becirovic et al.(2008)· Human Mutation

This case-control association study sequenced all 33 exons of NOTCH3 in 269 familial ischemic stroke probands and identified variants associated with ischemic stroke risk in Caucasian populations. The most significant finding was rs78501403 (p.R1560P, exon 25), which showed a protective effect against ischemic stroke (OR=0.50, P=0.0022) in the combined Caucasian series (721 cases, 1,004 controls). Additional findings included rs3815188 (p.T101T) associated with increased small-vessel stroke risk (P=0.008) and rs61749020 (p.P380P) associated with decreased large-vessel stroke risk (P=0.047).

Traits studied:Cardioembolic strokeIschemic strokeLarge-vessel ischemic strokeSmall-vessel ischemic stroke
PubMedDOIMetascience Observatory

About NOTCH3

This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]

View all NOTCH3 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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